CARDIOVASCULAR DETERMINANTS OF CATECHOLAMINE RELEASE

前列腺素E_2(PGE_2)全身给药的作用评价 前列腺素E_2静脉滴注和脑室-脑池中心滴注 在中枢调节中，血管紧张素II依赖，反射性地 急性肾无力犬肾上腺髓质兴奋性儿茶酚胺释放 是我们在下一个资助期的目标。在麻醉、肝素化的狗身上 急性肾切除加肾上腺-股分流术后 我们将研究静脉注射前列腺素E_2‘S的剂量效应 恢复正常肾上腺反射儿茶酚胺释放的能力 急性出血。适当的亚全身阈值剂量的前列腺素E_2 根据这些数据，然后我们将脑室-脑池PGE2灌流到 麻醉急性无肾犬以前列腺素E_2为阈值 出血后反射性儿茶酚胺释放。最后，我们会 脑室同时注入血管紧张素II和前列腺素E_2 明确前列腺素E_2对血管紧张素II反应性的中枢作用。 脑室-脑池灌注的前列腺素E_2将在两种不同的 在一组实验中，静脉注射血管紧张素和 脑室-脑池灌流的PGE2将在另一组中同时给予 实验中，前列腺素E_2和血管紧张素II将同时在 脑室-脑池灌流回路。了解神经激素 控制反射性儿茶酚胺的释放是一个长期目标；另一个 相关的目标是了解肾脏激素是否特别 肾素和在其影响下产生的血管紧张素II和前列腺素E_2 需要支持中枢神经系统的反射活动。这样的生理学 我们希望，洞察力将帮助我们理解紊乱的中枢神经 临床高血压的系统机制。

Evaluation of the role of Prostaglandin E2 (PGE2) delivered systemically as intravenously infused PGE2 and centrally by ventriculo-cisternal perfusion in controlling centrally mediated, Angiotensin II dependent, reflexly excited adrenal medullary catecholamine release in acutely anephric dogs are our goals for the next grant period. In anesthetized, heparinized dogs following acute nephrectomy and placement of adreno-femoral shunts and aortic cannulae we will study the dose responsiveness of intravenous PGE2's ability to restore normal adrenal reflex catecholamine release elicited by acute hemorrhage. With an appropriate sub-systemic threshold dose of PGE2 derived from that data, we then will perfuse ventriculo-cisternal PGE2 in anesthetized acutely anephric dogs with threshold quantities of PGE2 on reflex catecholamine release following hemorrhage. Finally, we will infuse, ventriculo-cisternally, Angiotensin II and PGE2 concomitantly to define the central effect of PGE2 on Angiotensin II responsiveness. Ventriculo-cisternally perfused PGE2 will be evaluated in two different ways; in one set of experiments, I.V. Angiotensin and ventriculo-cisternally perfused PGE2 will both be given and in another set of experiments, PGE2 and Angiotensin II will be given concominantly in the ventriculo-cisternal perfusion circuit. Understanding the neuro-hormonal control reflex catecholamine release is one long-term objective; another related goal is understanding whether or not renal hormones, specifically renin and the Angiotensin II generated under its infuence and PGE2, are needed to support central nervous system reflex activity. Such physiologic insights will, we hope, help us understand disordered central nervous system mechanisms involved in clinical hypertension.